This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Application of racemic protein crystallography to determine the X-ray structure of protein molecules which are otherwise difficult to crystallize. This involves the total chemical synthesis of native protein (i.e. L-protein) and 'enantiomer'(i.e. the mirror image D-protein molecule). Crystallization of a protein molecule from a racemic mixture (i.e. a solution containing equal proportions of L- and D- protein enantiomers) can lead to more facile formation of (centrosymmetric) crystals. The availability of centrosymmetric protein crystals in turn can facilitate ab initio structure solution by direct methods. We have recently demonstrated this racemic approach by producing the centrosymmetric protein crystals of snowflea antifreeze protein and crambin from our laboratory. To explore the general utility of this approach we wish to apply this method to other chemically synthesized proteins, such as: antimicrobial micro-protein plectasin, antifreeze type IV protein, and topological analogue of crambin. Elucidation of molecular details of HIV-1 protease catalysis, an important target in AIDS chemotherapy. Various chemical analogues were synthesized to perform 'dynamics/function'correlations in the catalytic mechanism;a totally artificial tunable catalytic apparatus was designed and incorporated into the enzyme molecule. Proper execution of such long-term research project involves extensive use of X-ray structural analysis using synchrotron facilities.